The North American-AIDS Cohort Collaboration on Research and Design (NA-ACCORD) has represented Region 1 of the leDEA initiative since 2006. The 22 single and multi-site clinical and classical epidemiologic HIV cohorts of the NA-ACCORD encompass most HIV/AIDS cohorts within the US and Canada. Over 200 sites in the US and Canada contribute data collected from 150,000 HIV-infected participants. We have established a strong collaborative infrastructure that capitalizes on the talents and expertise of multi-disciplinary group of investigators that span basic science, clinical research, epidemiology, data informatics and biostatistics. We have been highly productive in addressing our previous Aims and expanding our scientific focus to several areas of contemporary importance in HIV in North America, and our collaboration is well- positioned to answer the key questions in practice today. We have three broadly-defined aims for the next funding cycle: Aim 1: Assess and characterize the clinical course of HIV infection in North America, with a focus on aging, major non-AIDS comorbidities and life-expectancy. Aim 2: Characterize the HIV Care Continuum in North America from engagement in HIV care through viral suppression, and extend the Continuum to include long-term retention, utilization of ART to clinical outcomes and life-expectancy. Aim 3: Assess the impact of new direct-acting antivirals (DAAs) on the progression and outcomes of HIV and hepatitis C (HCV) disease in HIV-HCV co-infected persons. The NA-ACCORD is a world-class collaboration of established HIV cohorts well-positioned to provide definitive answers to these issues of contemporary relevance in the U.S. and Canada. In addition, we will expand our collaboration with other leDEA regions to both inform future experience in resource-limited regions as the treatment of the epidemics mature, and to identify and understand differences in treatment, outcomes and prognostic factors that might inform future research and clinical care globally.